We plan to continue studies of the metabolic fate and metabolic interactions (re: inducers, inhibitors and their own metabolites) of a number of drugs, many of them anticonvulsants or potential anticonvulsants: (a) primidone and its active metabolites, (b) phenobarbital, (c) N-alkyl and N,N'-dialkylbarbiturates and malonamides, (d) thiopental, (e) hexobarbital, (f) t-butethal, (g) secobarbital and barbital, (h) bufotenine and its O-methyl derivative. All have been and are to further studied in vivo and in vitro in mice and rats, using "standard" techniques. We will use the best quantitative analytical methodology we can devise, using solvent extraction, countercurrent distribution, thinlayer chromatography and liquid scintillation counting. All drugs with which we work have been or will be synthesized (by the writer) with C14 label and often with H2, N15 or C13, to facilitate quantitation and to aid in structure elucidation by gas chromatography-mass spectrometry (gc/ms). Additional studies, in man, are planned for compounds in categories (a), (b), and (h). We plan only oral administration (followed by analyses of blood and excreta) of primidone-ethyl-C14 and -ethyl d2. These will be carefully looked at with regard to blood levels and excretion of unchanged drug and its active metabolites (phenylethylmalonamide and phenobarbital) in normal volunteers and in selected patients on chronic primidone therapy. We are particularly interested to see if humans produce any unique metabolites. Bufotenine-C14,d3 and 5-methoxyindoleacetic acid-C14, d2 will be added to the urine of normal people and selected psychiatric patients and these compounds then isolated by methodology we devised for rats several years ago. Examination by gc/ms and specific ion monitoring (SIM) should gives a firm answer to the question as to whether or not these substances are in the urine. We will test several N, N'-dialkylmalonamides (which we will synthesize) for anticonvulsant activity in mice and rats. Continusing efforts will be made to improve and systematize solvent extraction and certain derivatization procedures, to facilitate the clean-up and quantitation of drugs and their metabolites by both "classical" methods and gc/ms/SIM.